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805: Creating Cell-Free Gene Editing On A Chip For Cancer Diagnosis and Treatment - Dr. Eric Kmiec
2025/3/24
People Behind the Science Podcast Stories from Scientists about Science, Life, Research, and Science Careers
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Eric Kmiec
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Marie McNeely
Marie McNeely: 我介绍了Eric Kmiec博士及其在基因编辑领域，特别是癌症治疗方面的开创性工作。他领导的基因编辑研究所致力于开发新的癌症疗法，重点是破坏导致癌细胞对抗化疗、放疗和免疫疗法产生耐药性的基因。
Eric Kmiec: 我从事的工作结合了教授和科学家的角色，既进行科学研究，也指导学生。我们专注于开发治疗癌症的新方法，特别是破坏导致癌细胞对抗化疗、放疗或免疫疗法产生耐药性的基因。我的工作也包括与临床医生合作，将基因编辑技术应用于癌症治疗。我的座右铭是：你不是根据你做了什么来评判，而是根据你为他人做了什么来评判。这激励着我致力于改善人们的健康状况。
在职业生涯中，Bruce Alberts教授教会我科学的重要性，而Nicholas Petrelli博士则帮助我建立了基因编辑研究所，并支持我们在癌症治疗领域应用基因编辑技术。
我的研究始于对真菌基因重组的研究，这为我后来的基因编辑研究奠定了基础。在基因编辑技术发展初期，我们面临着许多挑战，但我们坚持不懈，最终取得了成功。
我们开发了两种重要的基因编辑技术：一种是针对肺癌的基因编辑疗法，旨在减少化疗的毒性；另一种是体外基因编辑系统（“芯片上的基因编辑”），用于研究CRISPR-Cas9的工作机制，并与Novellus公司合作开发诊断方法。
此外，我们还将一个过时的研究系统改造成了一种基因编辑教学课程，用于高中、社区学院和四年制大学。
与高校、研究所和公司合作，有助于推动科学发展，并塑造我们对基因编辑的思考方式。
在职业生涯中，我经历过许多失败，但这些失败也让我吸取了宝贵的教训，最终促进了我的成功。
我儿子小时候无意中给我的建议，启发了我对RNA在基因编辑中作用的思考，这最终促进了CRISPR技术的开发。
我培养了许多优秀的学生，其中Brett Sandsbury是一位杰出的研究生，她的贡献推动了“芯片上的基因编辑”技术的进步。
我热爱阅读，最近读了Walter Isaacson写的达芬奇传记，从中我看到了艺术家和科学家创造过程的共通之处。
在冷泉港实验室与著名科学家交流的经历，让我对科学家的创造性思维方式有了更深的理解。
如果我有无限的资源，我会专注于解决公众对基因编辑的误解和担忧，并促进公众对基因编辑技术的理解和接受。
最好的建议是接受失败是学习过程的一部分，并从失败中吸取教训。
总而言之，我的研究生涯充满了挑战和机遇，我始终坚持不懈，致力于推动基因编辑技术在癌症治疗中的应用，并为公众教育和科学普及做出贡献。
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Eric Kmiec: I think I'd describe it really as the hybrid between a professor and a scientist. Teaching has always been important and I've had academic positions throughout my career where I've had the pleasure of actually teaching undergraduate and graduate students. But from the perspective of the daily work, it's really to do science and to advance that in a research group. And in particular, what we're focused on now is trying to develop a new way to treat cancer with a focus on trying to destroy the genes that cause resistance in standard therapy such as chemotherapy or radiation or immunotherapy.
Eric Kmiec: I think it really comes from my mother and I don't think she developed it or originated it, but it's really basically that you're not judged on what you do, but rather you're judged on what you do for others.
Eric Kmiec: One was a member of my PhD thesis committee, and that was Bruce Alberts, who went on to be a prominent member of the National Academy of Science, and I think eventually president of the National Academy. What I learned from Bruce is that science is what really sustains you....But Nick has a relatively important gift for vision and its ability to see what's on the horizon in new medical treatment. And I think about three years ago, we started talking about moving here as a research lab into the cancer center. And certainly there were naysayers that gene editing wouldn't flourish or anything. And we now call them members of the Flat Earth Society as well. But against all that backdrop, he actually helped us establish this gene editing institute.
Eric Kmiec: So it's been kind of at the center part of my career and something that we as a laboratory continue to do, and that's to study how chromosomes exchange information. It ultimately led to moving directly into gene editing....But obviously, when ThinkFinger Nucleases and Talons and CRISPR started to enter the scene, the whole field that was kind of working along on mechanism and regulation jumped into the main fray. And we have been able to kind of leverage our background and knowledge of the field as a whole and move into a cancer center where gene editing has to survive.
Eric Kmiec: So circling back to having a molecular medicine or gene editing technology in a complex situated inside a cancer center, we actually came in and began to focus on trying to develop ways in which we could use gene editing for cancer. I mean, it's the theme of the cancer center, obviously. So the The number one cancer killer in the state of Delaware and nationally is lung cancer. And shockingly, we actually have a small amount of research dollars per lung cancer death in the country....So the idea is to kind of couple and do a combinatorial approach where we actually destroy genes that are causing tumor cells to be resistant to chemotherapy. And while that sounds like low hanging fruit, it isn't, it's quite challenging. But it's actually a practical goal because we all want to make patients feel better and hopefully the tumor goes into remission. But patients that really suffer with the kind of treatments in cancer. So by focusing on that specific goal, we we actually are helping the quality of life while trying to move forward on treating them.
Eric Kmiec: We developed something that is akin to an in vitro gene editing system or gene editing on a chip, we like to call it, where we're actually looking at how CRISPR-Cas9 works in a controlled environment, meaning outside the cell....That actually led us to receive a BIRD grant, which is a grant that pairs Israeli biotechnology companies with American companies or researchers, and there are very few of them given on a yearly basis. But when we talked about this in vitro system, it turned out that a biotechnology company known as Novellus was actually doing a diagnostics and by pairing up with them, we were able to develop a strategy that would help them improve the precision and efficiency of a diagnostic assay they already are using.
Eric Kmiec: And it occurred to me that as gene editing with CRISPR starts to emerge fairly dramatically, we might actually be able to craft one of these systems for use in an undergraduate laboratory exercise, not only in a four-year college, but also at a community college and sometimes even at the high school level. So we worked with a group at a community college here in Delaware. It's actually the one that Vice President Biden's wife, Jill, has taught out in the past. And they were very excited about integrating a gene editing exercise. So we worked on it for a while. We put together a proposal and the National Science Foundation awarded us a grant to pursue this. So we've been able to take something that was really had gone past its use as a research system. and transformed it into an educational kid in curriculum for high school, community college, and four-year colleges.
Eric Kmiec: I think some of them drive the science. I've always liked to have an eye on the prize in that our goal in doing research is to make things work better and to contribute to therapies that will help people. And that can be all the way from developing a diagnostic or creating a cell line for someone who's testing a drug or to directly applying gene editing toward the development of a cancer therapy. So our relationships with these companies often help us even shape our basic way of thinking about things because there are great scientists in biotechnology companies and in pharmaceutical companies.
Eric Kmiec: There are too many of them, Marie, but I can give you one that is kind of an overview and And this is kind of how science sometimes work and it's not always pleasant. We started thinking about gene editing actually in the mid-90s to late 90s. And the reason for it was that was the boom days and the extremely booming part of gene therapy where a corrective gene was added to your favorite virus and injected into people and it was sent in to augment or replace the function of a disabled gene in a chromosome. And there were very good people working on that. Obviously, it was a huge field and billions of dollars were invested in it. But it always seemed to me that it was treating the symptom, not the problem. And so we began by saying, look, why don't we try to do gene repair? And in the old days, we call it gene repair. Now it's gene editing, which is, I think, a better term.
Eric Kmiec: So there's an old one and a new one. When the field was young, I was thinking about how RNA would actually participate in gene editing. It's actually a true story. We believed RNA, which is actually a major part, as you know, of the CRISPR complex, must be playing some role because there's so much of it. And it actually is one of the few pieces of single-stranded DNA that binds to DNA and can invade a helix because that's what transcription essentially does. But I couldn't figure out how to put the whole thing together. So, strangely enough, I was mowing the lawn with my oldest son. He was probably five or six at the time on my knee. And I was talking to him. I used to talk to him about the projects all the time. And he would give me great advice like, "I'm tired of listening to that," or, "That's stupid," or something. But then he kind of said something that said, "Well, why don't you just put DNA and RNA together and protein and buy protein to RNA?" And we started to kind of work on that and believe it or not, that's turned out to be what CRISPR is. Now, CRISPR was obviously in bacterial cells. So that little comment by Tyler actually pushed us in a direction. So that was an unexpected one. And then the second one, which is current, is the great pledge. And Marie, I'm sure you've experienced this, that every once in a while, a student comes along who comes into your lab, who just is the right student with the right hands on the right project. And The most recent development of this gene editing on a chip, this in vitro system, is being handled by a terrific young graduate student, Brett Sandsbury.
Eric Kmiec: I've always tried to have sort of a diverse interest in reading, and my wife is a very, very big reader, and I wish I read half as many books as she does. But I've always been kind of fascinated by biographies written by true historians, not sort of fictional writers that then pose as historians, but people who really dig in and are good writers. Ultimate historical papers that are published in journals are too deep for me and can really sort of knock you out. But I recently read a book by Walter Isaacson. It's the new biography of Leonardo da Vinci. Obviously, nothing needs to be said about da Vinci in terms of his impact and his genius. But it was interesting to read because Isaacson did not just relay the facts about where he was, what he did, although that's in the book. It was more about what inspired him. And the thing that struck me about da Vinci within this book was that it actually kind of followed the scientific method.
Eric Kmiec: Well, when I was a graduate student, actually, I used to go to Cold Spring Harbor and attend the meetings. They were long. They were six, seven days of very heavy science. But one of the great things about Cold Spring Harbor was you kind of walk around the corner and there would be James Watson standing or Frank Stahl or Charles Ratting, the pillars of genetic recombination and the Great East Group that was there forever. for many, many years with Amar Klar and Jester Thurn. So I had a number of opportunities to kind of sit and walk and listen to Watson talk about the creative process.
Eric Kmiec: Well, I'd ask my friend who's an orthopedic surgeon to repair my shoulder so I could play in the men's league in Pennsylvania. But beyond that, I think gene editing is at a really interesting point. And thinking about this question now, I think it's such a unique topic that it will engage a lot of people, ethicists, lawyers, and even insurance executives. I tend to step back from this technology a little bit and ask, let's assume that things go great. Let's assume that there's enough money to develop this and with your proffer there. If that is, that's great. But if we actually build something in research, will anyone come and use it? And the answer to that is not as easy as you might think. The general public needs to be educated that gene editing is not going to create four-headed salamanders or... Frankensteins, yeah, right. I say something like that and Hollywood drops this Wolf Eagle something on their movie Rampage out of the sky. So you're battling commercial entertainment. And I think that movie actually does mention CRISPR. So that's always great to hear. So there's a public perception about gene editing that's extremely important to control.
Eric Kmiec: Well, I grew up in a sports environment and I think the almost tough love advice, which may or may not be appropriate today, but I think if you spin it in this way, it actually makes some sense. And that you have to accept failure as part of the learning process. And it's how you respond to failure that will enable you to succeed in the future.
Deep Dive
Dr. Kmiec enjoys playing baseball and hockey, and he still plays baseball competitively in a league in Philadelphia. He also spends much of his time doing landscaping and yard work.
- Enjoys playing baseball and hockey
- Still plays competitive baseball
- Spends time landscaping and yard work
Shownotes Transcript